孙沙梅

自身免疫异常在自身免疫性肾病的发生和进展中起着至关重要作用，免疫调节是治疗这些疾病的重要策略。过去治疗自身免疫性肾病主要依靠激素和免疫抑制剂。然而随着对自身免疫性肾病发病机制的深入探索和生物医学研究的快速发展，生物制剂如泰它西普等，已越来越多地应用于肾脏疾病。现如今，我们对免疫介导的肾脏疾病发病机制的理解不断取得快速进展，这一进展最终导致了多种治疗药物的开发，这些药物持续改善了肾脏患者的预后。生物制剂是具有明确靶向性的单克隆抗体或抗体融合蛋白类生物大分子药物。已广泛用于自身免疫性疾病，其具有显著的疗效，可降低疾病并发症及死亡率。在这篇综述中，我们重点关注免疫介导的肾脏疾病的发病机制和治疗进展。

自身免疫性肾病；B细胞；泰它西普；生物制剂

[1] YE X, ZHOU X J, ZHANG H. Autophagy in Immune-Related Renal Disease [J]. J Immunol Res, 2019, 2019: 5071687. [2] HUNTER R W, WELSH N, FARRAH T E, et al. ANCA associated vasculitis [J]. Bmj, 2020, 369: m1070. [3] GORENJAK M. 4. Kidneys and Autoimmune Disease [J]. Ejifcc, 2009, 20(1): 28-32. [4] ALMAANI S, MEARA A, ROVIN B H. Update on Lupus Nephritis [J]. Clin J Am Soc Nephrol, 2017, 12(5): 825-35. [5] HOLDSWORTH S R, GAN P Y, KITCHING A R. Biologics for the treatment of autoimmune renal diseases [J]. Nat Rev Nephrol, 2016, 12(4): 217-31. [6] HIEPE F, RADBRUCH A. Plasma cells as an innovative target in autoimmune disease with renal manifestations [J]. Nat Rev Nephrol, 2016, 12(4): 232-40. [7] SHABGAH A G, SHARIATI-SARABI Z, TAVAKKOL-AFSHARI J, et al. The role of BAFF and APRIL in rheumatoid arthritis [J]. J Cell Physiol, 2019, 234(10): 17050-63. [8] SUáREZ-FUEYO A, BRADLEY S J, KLATZMANN D, et al. T cells and autoimmune kidney disease [J]. Nat Rev Nephrol, 2017, 13(6): 329-43. [9] DAVIDSON A. What is damaging the kidney in lupus nephritis [J]. Nat Rev Rheumatol, 2016, 12(3): 143-53. [10] HANLY J G, O'KEEFFE A G, SU L, et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study [J]. Rheumatology (Oxford), 2016, 55(2): 252-62. [11] ARKATKAR T, DU S W, JACOBS H M, et al. B cell-derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity [J]. J Exp Med, 2017, 214(11): 3207-17. [12] D'AMICO G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome [J]. Semin Nephrol, 2004, 24(3): 179-96. [13] SCHENA F P, NISTOR I. Epidemiology of IgA Nephropathy: A Global Perspective [J]. Semin Nephrol, 2018, 38(5): 435-42. [14] SUZUKI H. Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis [J]. Clin Exp Nephrol, 2019, 23(1): 26-31. [15] RIZK D V, MAILLARD N, JULIAN B A, et al. The Emerging Role of Complement Proteins as a Target for Therapy of IgA Nephropathy [J]. Front Immunol, 2019, 10: 504. [16] CHUNG E Y M, WANG Y M, KEUNG K, et al. Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment [J]. Front Immunol, 2022, 13: 1036249. [17] SALHI S, RIBES D, FORTENFANT F, et al. Plasma cell-directed therapy for rituximab-refractory PLA2R+ membranous nephropathy [J]. Nephrol Dial Transplant, 2023, 38(12): 2851-3. [18] BECK L H, JR., BONEGIO R G, LAMBEAU G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy [J]. N Engl J Med, 2009, 361(1): 11-21. [19] XU X, WANG G, CHEN N, et al. Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China [J]. J Am Soc Nephrol, 2016, 27(12): 3739-46. [20] HOXHA E, STAHL R A. Membranous Nephropathy: The Journey Continues … [J]. EBioMedicine, 2015, 2(5): 374-5. [21] FARQUHAR M G, VERNIER R L, GOOD R A. An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus [J]. J Exp Med, 1957, 106(5): 649-60. [22] LV J, LIU L, HAO C, et al. Randomized Phase 2 Trial of Telitacicept in Patients With IgA Nephropathy With Persistent Proteinuria [J]. Kidney Int Rep, 2023, 8(3): 499-506. [23] CAI J, GAO D, LIU D, et al. Telitacicept for autoimmune nephropathy [J]. Front Immunol, 2023, 14: 1169084. [24] SALAZAR-CAMARENA D C, ORTIZ-LAZARENO P C, CRUZ A, et al. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus [J]. Lupus, 2016, 25(6): 582-92. [25] LI W, PENG X, LIU Y, et al. TLR9 and BAFF: their expression in patients with IgA nephropathy [J]. Mol Med Rep, 2014, 10(3): 1469-74. [26] DU Y, LI J, HE F, et al. The diagnosis accuracy of PLA2R-AB in the diagnosis of idiopathic membranous nephropathy: a meta-analysis [J]. PLoS One, 2014, 9(8): e104936. [27] ZHANG L, JIN H, WANG D, et al. Case report: Successful treatment of refractory membranous nephropathy with telitacicept [J]. Front Immunol, 2023, 14: 1268929. [28] LI S, DING L, YANG Y J, et al. Telitacicept for minimal change disease [J]. Kaohsiung J Med Sci, 2023, 39(7): 748-9. [29] SHI F, XUE R, ZHOU X, et al. Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease [J]. Immunopharmacol Immunotoxicol, 2021, 43(6): 666-73.

点击下载PDF